This grant application requests support the continued participation of the Memorial Sloan-Kettering Cancer Center and its affiliate hospitals in the research protocols of the Childrens Cancer Group. The clinical studies are designed to improve the survival of children with cancer through multidisciplinary randomized, collaborative treatment protocols that are stratified to the patients' stages of disease and their prognostic groups. Whenever possible the treatments are reduced to minimize both short and long-term toxicity. Epidemiologic studies are conducted to study the incidence, natural history and possible causes of childhood malignancies. Laboratory studies will be conducted to study the biology of cancer cells and correlate these with the clinical variables. The aims of our participation and those of CCG are a) to provide large numbers of patients for groupwide studies in order to make multiarm, randomized, prospective studies possible, b) to utilize the scientific leadership, expertise and clinical experience of Pediatric Oncologists and other experts at MSKCC to help design and implement new studies, and c) to contribute scientific and administrative expertise and experience to Standing Committees of CCG. Clinical studies at MSKCC will continue in the evaluation and development of new chemotherapeutic agents for patients who become refractory to conventional therapy. Pharmacologic studies will evaluate drug metabolism and correlate it with therapeutic response. Studies will be conducted in the role of bone marrow transplantation in hematopoietic disorders and refractory solid tumors. The extensive clinical facilities of MSKCC with its well developed intensive supportive care program and its research laboratories will make it possible to develop novel treatment protocols. They will be piloted and made available for groupwide randomized prospective trials. The clinical personnel of MSKCC have extensive and proven experience in the design and implementation of innovative treatment protocols that have been adopted worldwide. They will continue to provide leadership for CCG in study committees and strategy groups. Current pilot studies at MSKCC that will become available for CCG use during this grant period include protocol for high-risk ALL, a retrieval protocol for refractory Hodgkin's disease, a new CNS leukemia therapy, a new osteogenic sarcoma protocol and a monoclonal antibody treatment for neuroblastoma. Members of the affiliate hospitals have been participating in CCG studies and have proven their ability to conduct the clinical studies and provide material for laboratory evaluation.